Blue light (lambda=453 nm) nitric oxide dependently induces beta-endorphin production of human skin keratinocytes in-vitro and increases systemic beta-endorphin levels in humans in-vivo

摘要

beta-Endorphin exerts a broad spectrum of physiological activity on mood, immune functions, pain management, reward effects, and behavioral stability. beta-Endorphin is produced in certain neurons within the central and peripheral nervous system but also in the skin, especially in response to ultraviolet radiation. In the present study we have investigated the impact of visible blue light at lambda = 453 nm (BL) on beta-endorphin production of primary human skin keratinocytes (hKC) in-vitro as well as on systemic beta-endorphin formation of whole-body exposed subjects in-vivo. We found that BL irradiation significantly enhanced both keratinocytic beta-endorphin production of hKC cultures as well as systemic beta-endorphin concentrations in light exposed healthy subjects. Interestingly, in hKC cultures elevated beta-endorphin formation was paralleled by significantly increased levels of non-enzymatically generated nitric oxide (NO), whereas elevated systemic beta-endorphin values of BL-exposed subjects were accompanied by enhanced systemic concentration of bioactive NO-derivates. These findings point to a pivotal role of NO in the molecular mechanism of the observed BL-induced effects, and indeed, exogenously applied NO was able to significantly enhance beta-endorphin production in hKC cultures. Thus, our finding of BL-induced increases in systemic beta-endorphin concentration in-vivo can be plausibly explained by an event sequence comprising 1.) BL-driven non-enzymatic formation of NO in the exposed skin tissue, 2.) systemic distribution of cutaneously produced NO in the form of bioactive nitroso compounds, 3.) a subsequent NO-dependent induction of beta-endorphin synthesis in epidermal keratinocytes, and 4.) probably also a NO-dependent modulation of beta-endorphin synthesis in specialized neurons within the central and peripheral nervous system.